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GSK3ß-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration.
Wang, Youpei; Zheng, Xiang; Wang, Qing; Zheng, Meiqin; Pang, Lingxia.
Afiliación
  • Wang Y; Clinical Examination Center, The Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • Zheng X; Emergency Department of Children, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • Wang Q; Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou, 325305, China.
  • Zheng M; Clinical Examination Center, The Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • Pang L; Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou, 325305, China. Electronic address: plx@wmu.edu.cn.
Biochem Biophys Res Commun ; 531(4): 543-551, 2020 10 22.
Article en En | MEDLINE | ID: mdl-32807499
Previous studies showed that the activation of Wnt signaling reduced high glucose (HG)-mediated fibroblast damage, but the molecular basis for this phenomenon remains elusive. This study aimed to analyze the level of phosphorylation of GSK3ß Ser9 (pGSK3ß Ser9) during HG damage. Moreover, the phosphomimic form of pGSK3ß Ser9 was expressed to analyze its effect on cell migration via the phosphorylation of Ikaros. The results revealed that HG treatment significantly reduced the pGSK3ß Ser9 level. The overexpression of GSK3ß Ser9D and GSK3ß Ser9A accelerated and inhibited fibroblast cell migration, respectively. P110α knockdown or treatment with SP600125, an inhibitor of JNK, also reduced the pGSK3ß Ser9 level under HG condition. Treatment with SP600125 inhibited the migration of fibroblasts, but not in GSK3ß Ser9D-expressing cells. Further, yeast two-hybrid screening and biochemical analysis identified that GSK3ß interacted and phosphorylated Ikaros at Ser391. Besides, GSK3ß Ser9D, but not GSK3ß Ser9A, activated Ikaros Ser391 phosphorylation. Expressing Ikaros or ß-catenin significantly promoted cell migration, suggesting that GSK3ß modulated cell migration partially via the activation of Ikaros besides ß-catenin signaling under HG condition. The expression of the phosphomimic form of Ikaros Ser391D resulted in a significant increase in the extent of cell migration compared with Ikaros under HG condition. Moreover, the Ikaros Ser391D DNA-binding affinity toward the ANXA4 promoter increased, and ANXA4 suppression promoted cell migration. In conclusion, the results of this study provided a new regulatory mechanism by which GSK3ß negatively regulated human skin fibroblast cell migration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A4 / Factor de Transcripción Ikaros / Fibroblastos / Glucógeno Sintasa Quinasa 3 beta Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anexina A4 / Factor de Transcripción Ikaros / Fibroblastos / Glucógeno Sintasa Quinasa 3 beta Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos